1. Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA;
J Cancer. 2013;4(3):251-61. doi: 10.7150/jca.5838. Epub 2013 Mar 15.
The process of neoplastic transformation of the colon involves a progression through hyperproliferative epithelium through the aberrant crypt foci→small adenoma→large adenoma→invasive cancer→metastatic disease. These are orchestrated by sequential genetic and epigenetic events which provide the underpinnings of cellular alterations such as early induction in proliferation/suppression of apoptosis, along with the late stage increase in invasiveness. Colorectal cancer (CRC) averages 49-111 mutations per tumor encompassing 10-15 critical signaling pathways[1]. Accumulating such a high number of mutations requires a fertile mutational field, which is the hallmark of colon carcinogenesis.While genetic susceptibility to colorectal cancer is well-known, at least half of the risk is believed to be due to exogeneous factors (e.g., obesity, diet, exercise). Understanding these risk factors represents a promising mode of tailoring screening modality and intensity. However, previous attempts using these factors (i.e., NCI risk calculator) have only been modestly successful with an area under receiver operating characteristics (ROC) curve (AUC) of just 0.61. One of the most important concepts is that risk is the interaction between these genetic and environmental components and is driven by the variety of polymorphisms. Thus, predicting risk is difficult given the complexity. On the other hand, the colonic mucosa represents the end product of the complex interplay between these multiple factors. The power of field carcinogenesis is that it reflects this interplay between genetics and environment.
结肠的肿瘤转化过程涉及通过异常隐窝病灶→小腺瘤→大腺瘤→浸润性癌→转移性疾病的增殖上皮的进展。这些是由顺序的遗传和表观遗传事件协调的，这些事件为细胞改变提供了基础，例如早期诱导增殖/抑制细胞凋亡，以及晚期侵袭性增加。结直肠癌（CRC）平均每个肿瘤有 49-111 个突变，包括 10-15 个关键信号通路[1]。积累如此多的突变需要一个肥沃的突变场，这是结肠癌发生的标志。虽然对结直肠癌的遗传易感性是众所周知的，但至少一半的风险被认为是由于外源性因素（例如肥胖、饮食、运动）。了解这些危险因素代表了一种有前途的定制筛查模式和强度的模式。然而，以前使用这些因素（即 NCI 风险计算器）的尝试仅取得了适度的成功，受体操作特征（ROC）曲线下面积（AUC）仅为 0.61。一个最重要的概念是，风险是这些遗传和环境因素之间的相互作用，由多种多态性驱动。因此，鉴于其复杂性，预测风险是困难的。另一方面，结肠黏膜代表这些多种因素之间复杂相互作用的最终产物。场致癌的力量在于它反映了遗传和环境之间的这种相互作用。
